Background Anaphylaxis is a severe, potentially life‐threatening allergic reaction driven primarily by the activation of mast cells. We still fail to understand factors underlying reaction severity. Furthermore, there is currently no reliable diagnostic test to confirm anaphylaxis in the emergency department (ED). Objective This study sought to explore gene expression changes associated with anaphylaxis severity in peripheral blood leucocytes and evaluate biomarker potential. Methods Microarray analysis (total RNA) was performed using peripheral blood samples from ED patients with moderate (n = 6) or severe (n = 12) anaphylaxis and sepsis (n = 20) at presentation (T0) and one hour later (T1). Results were compared between groups and healthy controls (n = 10 and n = 11 matched to anaphylaxis and sepsis patients, respectively). Changes in gene expression were determined using R programming language, and pathway analysis applied to explore biological processes and pathways associated with genes. Differentially expressed genes were validated in an independent cohort of anaphylaxis (n = 30) and sepsis (n = 20) patients, and healthy controls (n = 10), using quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR). Results Significant up‐regulation of small nucleolar RNAs (snoRNAs) was demonstrated in anaphylaxis compared to sepsis patients in the microarray cohort, at T0 and T1. qRT‐PCR analysis of the validation cohort showed five genes: SNORD61, SNORD8, SNORD69, SNORD119 and HIST1H1D to be significantly up‐regulated (adjusted p < 0.05) in severe anaphylaxis compared to sepsis. Seven genes (SNORD61, SNORD8, SCARNA21, SNORD69, SNORD110, SNORD119 and SNORD59A) were significantly up‐regulated (adjusted p < 0.05) in severe anaphylaxis compared to healthy controls. Conclusion This study demonstrates for the first time the unique involvement of snoRNAs in the pathogenesis of anaphylaxis and suggests they are not a general feature of systemic inflammation. Further investigation of snoRNA expression in anaphylaxis could provide insights into disease pathogenesis. Clinical relevance SnoRNAs are up‐regulated during acute anaphylaxis in humans and could potentially be used as biomarkers of severe anaphylaxis.

Objective. Mechanisms underlying the anaphylactic reaction in humans are not fully understood. Here, we aimed at improving our understanding of anaphylaxis by investigating gene expression changes. Methods. Microarray data set GSE69063 was analysed, describing emergency department (ED) patients with severe anaphylaxis (n = 12), moderate anaphylaxis (n = 6), sepsis (n = 20) and trauma (n = 11). Samples were taken at ED presentation (T0) and 1 h later (T1). Healthy controls were age and sex matched to ED patient groups. Gene expression changes were determined using limma, and pathway analysis applied. Differentially expressed genes were validated in an independent cohort of anaphylaxis patients (n = 31) and matched healthy controls (n = 10), using quantitative reverse transcription-polymerase chain reaction. Results. Platelet aggregation was dysregulated in severe anaphylaxis at T0, but not in moderate anaphylaxis, sepsis or trauma. Dysregulation was not observed in patients who received adrenaline before T0. Seven genes (GATA1 (adjusted P-value = 5.57 9 10 À4 ), TLN1 (adjusted P-value = 9.40 9 10 À4 ), GP1BA (adjusted P-value = 2.15 9 10 À2 ), SELP (adjusted P-value = 2.29 9 10 À2 ), MPL (adjusted P-value = 1.20 9 10 À2 ), F13A1 (adjusted P-value = 1.39 9 10 À2 ) and SPARC (adjusted P-value = 4.06 9 10 À2 )) were significantly downregulated in severe anaphylaxis patients who did not receive adrenaline before ED arrival, compared with healthy controls. One gene (TLN1 (adjusted P-value = 1.29 9 10 À2 )) was significantly downregulated in moderate anaphylaxis patients who did not receive adrenaline before ED arrival, compared with healthy controls. Conclusion. Downregulation of genes involved in platelet aggregation and activation is a unique feature of the early anaphylactic reaction not previously reported and may be associated with reaction severity.